<p><b><i>Backgroud/Aims:</i></b> The effects of rapamycin (RPM) on wound
healing have been previously studied. However, reciprocal contradictory
data have been reported, and the underlying mechanism remains unclear.
This study aims to uncover differential role of RPM in regulation of
wound healing and explore the possible mechanism. <b><i>Methods:</i></b>
C57BL/6J mice and epidermal cells were treated with different doses of
RPM. The wound re-epithelialization was observed by hematoxylin and
eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by
immunohistochemistry and quantitative real-time PCR. Epidermal cell
survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2
pathway were examined by western blot analysis. <b><i>Results:</i></b>
This study showed that differential doses of RPM could lead to separate
consequences in epidermis. Histological analyses showed that low-dose
RPM promoted wound healing, and enhanced the expression of IL-15 and
IGF-1. Furthermore, western blot analysis showed that the effect of
low-dose RPM in epidermis were not through mTORC1 pathway. Instead,
activation of the Akt/mTORC2 pathway was involved in low-dose
RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM
inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1
and mTORC2 pathway. <b><i>Conclusion:</i></b> This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.</p>